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| Status |
Public on Oct 21, 2020 |
| Title |
Cell-specific Characterization of the Placental Methylome |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs. Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
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| Overall design |
Placental tissues were obtained with approval from the University of British Columbia / Children’s and Women’s Health Centre of British Columbia Research Ethics Board (H04-70488, H16-02280, H13-00640). Women for a scheduled C-section with a healthy term (>37 weeks) singleton pregnancy were recruited with written informed consent at BC Women’s Hospital, Vancouver Canada. In addition, first trimester samples from elective terminations were obtained in a deidentified manner. A total of 9 first trimester (6.4-13 weeks) and 19 term (36.4-40.4 weeks) placental samples were obtained; all were screened for large chromosome abnormalities using CNV calling on the EPIC array, and found to be normal. No gross pathologies were noted. CS refers to fluorescense-activated cell-sorted samples, and enz refers to enzymatically separated trophoblast samples.
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| Contributor(s) |
Yuan V, Hui D, Yin Y, Peñaherrera MS, Beristain AG, Robinson WP |
| Citation(s) |
33407091 |
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| Submission date |
Oct 19, 2020 |
| Last update date |
Jan 11, 2021 |
| Contact name |
Wendy Robinson |
| E-mail(s) |
wprobinsonlab@gmail.com
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| Organization name |
University of British Columbia
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| Department |
Medical Genetics
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| Lab |
Robinosn
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| Street address |
950 W 28th Ave
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (131)
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| Relations |
| BioProject |
PRJNA669992 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159526_RAW.tar |
161.2 Mb |
(http)(custom) |
TAR |
| GSE159526_detp.csv.gz |
148.9 Mb |
(ftp)(http) |
CSV |
| GSE159526_unprocessed_meth.csv.gz |
242.0 Mb |
(ftp)(http) |
CSV |
| GSE159526_unprocessed_unmeth.csv.gz |
252.0 Mb |
(ftp)(http) |
CSV |
| Processed data included within Sample table |
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